CFTR regulates phagosome acidification in macrophages and alters bactericidal activity

• Published in: Nature cell biology Vol. 8; no. 9; pp. 933 - 944
• Main Authors: Nelson, Deborah J, Di, Anke, Brown, Mary E, Deriy, Ludmila V, Li, Chunying, Szeto, Frances L, Chen, Yimei, Huang, Ping, Tong, Jiankun, Naren, Anjaparavanda P, Bindokas, Vytautas, Palfrey, H. Clive
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.09.2006; Nature Publishing Group
• Subjects: Acidification; Animal models in research; Animals; Bacteria; Biomedical and Life Sciences; Cancer Research; Cell Biology; Chloride channels; Cyclic AMP - physiology; Cystic Fibrosis Transmembrane Conductance Regulator - biosynthesis; Cystic Fibrosis Transmembrane Conductance Regulator - genetics; Cystic Fibrosis Transmembrane Conductance Regulator - physiology; Developmental Biology; Genes; Humans; Hydrogen-Ion Concentration; In Vitro Techniques; Ion Channel Gating; Life Sciences; Lysosomes - physiology; Macrophages; Macrophages - metabolism; Macrophages - microbiology; Macrophages - physiology; Macrophages, Alveolar - metabolism; Macrophages, Alveolar - microbiology; Macrophages, Alveolar - physiology; Macrophages, Peritoneal - metabolism; Macrophages, Peritoneal - physiology; Mice; Mice, Inbred C57BL; Mice, Knockout; Microbial Viability; Neutrophils - metabolism; Neutrophils - physiology; Phagocytosis; Phagocytosis - physiology; Phagosomes - physiology; Physiological aspects; Pseudomonas aeruginosa - physiology; Respiratory Burst; Stem Cells
• ISSN: 1465-7392; 1476-4679
• DOI: 10.1038/ncb1456

Acidification of phagosomes has been proposed to have a key role in the microbicidal function of phagocytes. Here, we show that in alveolar macrophages the cystic fibrosis transmembrane conductance regulator Cl − channel (CFTR) participates in phagosomal pH control and has bacterial killing capacity. Alveolar macrophages from Cftr −/− mice retained the ability to phagocytose and generate an oxidative burst, but exhibited defective killing of internalized bacteria. Lysosomes from CFTR -null macrophages failed to acidify, although they retained normal fusogenic capacity with nascent phagosomes. We hypothesize that CFTR contributes to lysosomal acidification and that in its absence phagolysosomes acidify poorly, thus providing an environment conducive to bacterial replication.